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April 30, 2018 -- The presence of amyloid on PET scans may be a sign that adults with no symptoms of dementia are still at risk of mild cognitive impairment or even Alzheimer's disease in the future as they age, according to a study published online April 30 in JAMA Neurology.

In the study, researchers from the Mayo Clinic in Rochester, MN, conducted PET scans with carbon-11-labeled Pittsburgh Compound B (PiB-PET). They found that adults ages 50 to 59 who had amyloid were twice as likely to develop dementia by the time they reached their 80s, compared with age-matched counterparts with no signs of amyloid accumulation. In addition, women with amyloid-positive PiB-PET results were more likely to develop cognitive impairment later in life than men.

"Our estimates of progression [from] amyloid-positive, cognitively unimpaired status to amnestic mild cognitive impairment may provide reliable and valid information from a population-based study for estimating the outcome of a successful antiamyloid therapeutic agent on a general North American population," wrote lead author Dr. Rosebud Roberts and colleagues.

Amyloid accumulation

There has been increasing evidence that elevated levels of amyloid in the brain are associated with an increased risk of Alzheimer's disease and could be the first preclinical sign of the illness. The same amyloid benchmark has been used to evaluate the risk of looming cognitive impairment and/or dementia in people with no signs of dementia.

"Despite this, there are relatively few population-based estimates of amyloid positivity in the population without dementia," the authors noted. "Our first objective was therefore to estimate the prevalence of amyloid positivity in a population without dementia."

A total of 1,671 participants (mean age, 71.3 ± 9.8 years) without dementia underwent amyloid PiB-PET imaging between August 2008 and September 2017. The group included individuals who were concerned that cognitive deficiencies may be developing, despite essentially normal functional activities and no clinical evidence of dementia. Among the subjects, 470 (28%) carried the ε4 version of the apolipoprotein E (APOE) genotype and 179 (11%) had prevalent mild cognitive impairment (JAMA Neurol, April 30, 2018).

Subjects had their first PET amyloid scans beginning in 2008 with four five-minute exams acquired 40 to 60 minutes after injection of PiB. Their clinical and cognitive evaluations continued every 15 months after the initial scans until September 2017.

The researchers also divided the subjects into four 10-year age groups, beginning with age 50. Amyloid positivity was based standardized uptake value ratios (SUVRs) greater than 1.42 on the PET scans.

Elevated risks

Subjects with amyloid-positive PET scans had a 2.3-fold increase in their risk of developing amnestic mild cognitive impairment, compared with those who had negative amyloid results, the researchers found. In addition, these same amyloid-positive adults had 1.9 times the risk of developing clinically diagnosed Alzheimer's versus their amyloid-negative counterparts.

Value of PiB-PET amyloid scans for predicting cognitive decline

Amyloid-negative

Amyloid-positive

No. with no cognitive impairment progressing to amnestic MCI

44 (4.2%)

63 (14.5%)

No. with no cognitive impairment progressing to Alzheimer's

3 (0.3%)

14 (3.2%)

No. with amnestic MCI progressing to Alzheimer's

10 (14.5%)

36 (32.7%)

MCI = mild cognitive impairment

The prevalence of amyloid among subjects with no cognitive impairment and no dementia also increased from their baseline PiB-PET scans to when they reached their 80s, from 2.7% to 41.3%. Interestingly, the prevalence of amyloid was greater among women than men as the participants aged.

Amyloid prevalence, men vs. women with no cognitive impairment

Age

Men

Women

50-59

1.9%

3.5%

60-69

13.6%

22.4%

70-79

32.6%

31.6%

80-89

33.0%

47.6%

"Despite the nonsignificant associations by sex for incident Alzheimer's dementia, the higher prevalence of amyloid positivity in women and sex differences in risk of progression for amyloid-positive individuals who are either cognitively unimpaired or have mild cognitive impairment may have implications for reporting clinical trial results by sex," the authors wrote. "Although we did not find a significant interaction of amyloid positivity with sex, higher rates of progression in amyloid-positive women with mild cognitive impairment compared with men may be partly because of the higher prevalence of amyloid positivity in women."

Roberts and colleagues cited the large sample size, high prevalence of amyloid positivity, and population-based, natural history design as strengths of the study, adding that the prospective approach and "high retention of participants provide reliable and valid information on longitudinal outcomes."

"The study findings may be informative for [the] design of primary and secondary Alzheimer's disease prevention trials," they wrote. "The sex differences in outcomes remain to be validated."